Edward A. Fon

GALC variants affect Glucocerebrosidase to Galactosylceramidase activity ratio

The paper examines how genetic variants in GALC affect the ratio of glucocerebrosidase to galactosylceramidase activity and its association with Parkinson's disease risk.

USP15 REGULATES NEUROINFLAMMATION AND DRIVES PATHOGENESIS IN SYNUCLEINOPATHIES

This study shows that USP15 deletion in astrocytes and microglia reduces neuroinflammation and slows synucleinopathy progression in mice, with human data linking USP15 expression to Parkinson's disease risk.

An automated workflow for quantifying the formation of synuclein aggregates in human dopaminergic neurons

This paper develops an automated assay to quantify synuclein aggregate formation in human dopaminergic neurons using pS129-syn as a marker, showing dose- and time-dependent increases with PFFs and genetic factors affecting aggregate formation.

N-terminal acetylation reduces α-synuclein pathology in models of Parkinson's disease

This study shows that N-terminal acetylation of α-synuclein reduces aggregation, uptake, seeding, and toxicity in Parkinson's disease models.

A high-content imaging workflow to screen for molecules that reduce cellular uptake of α-synuclein preformed fibrils

The paper describes a high-content imaging assay to screen small molecules that reduce cellular uptake of α-synuclein preformed fibrils in hiPSC-derived cells, identifying compounds that effectively lower intracellular PFF load.

STIP1/HOP Promotes the Formation of Cytotoxic α-Synuclein Oligomers

This study identifies how STIP1/HOP interacts with a-Syn to promote toxic oligomer formation in synucleinopathies.

WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease

This study identifies WDR44 as a driver of de novo α-synuclein aggregation at the lysosomal membrane, linking early aggregation events to neuronal dysfunction in Parkinson's Disease.

Integration of iPSC-derived microglia into human midbrain organoids enhances microglial maturation and inflammatory signaling

This study integrates iPSC-derived microglia into human midbrain organoids to enhance microglial maturation and inflammatory signaling, revealing altered transcriptional signatures in dopaminergic neurons and astrocytes.

Machine learning and burden analyses highlight novel candidate genes in Parkinson's disease

The paper integrates machine learning and rare variant burden analysis to identify novel candidate genes for Parkinson's disease.

TMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations.

This study identifies genetic associations between lysosomal genes and Parkinson's disease risk across diverse populations using GWAS and whole genome sequencing data.

α-Synuclein purification significantly impacts seed amplification assay performance and consistency

This study compares four methods of purifying α-synuclein for seed amplification assays, finding that osmotic shock-purified monomer has the lowest aggregation propensity and best inter-batch reproducibility.

Substrate recognition by the human mitochondrial processing peptidase and its processing of PINK1

This study investigates how the human mitochondrial processing peptidase (MPP) recognizes and processes the N-terminal targeting sequence of PINK1, revealing its binding mechanism and functional implications.

LRRK2 Kinase Mediates Increased GCase Activity in Microglia in Response to Proinflammatory Stimuli

This study investigates how LRRK2 kinase activity affects GCase activity in microglia under inflammatory conditions, finding that LRRK2 variants influence GCase response to interferon gamma.

A validated antibody toolbox for ALS research

The paper establishes a validated antibody platform for ALS research, identifying high-quality antibodies and revealing protein expression patterns in neurological cell types.

In vivo and in silico alpha-synuclein propagation dynamics: The role of genotype, epicentre, and connectivity

This study investigates how alpha-synuclein propagation affects brain atrophy and motor deficits across different genotypes and inoculation sites in mice.

Ensemblex: an accuracy-weighted ensemble genetic demultiplexing framework for population-scale scRNAseq sample pooling

Ensemblex improves accuracy in genetic demultiplexing of pooled scRNA-seq samples by combining four algorithms with accuracy weighting.

Insights into Ancestral Diversity in Parkinsons Disease Risk: A Comparative Assessment of Polygenic Risk Scores

This study compares polygenic risk scores for Parkinson's disease across seven ancestries, finding varying predictive accuracy and highlighting the need for ancestry-specific models.

Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of α-synuclein aggregation

The paper uses CRISPR screens to identify OXR1 and EMC4 as modifiers of α-synuclein aggregation in Parkinson's disease and related synucleinopathies.

T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson's disease

The paper examines T cell responses to PINK1 and α-synuclein in prodromal Parkinson's disease, finding elevated reactivity comparable to clinically diagnosed PD.

Midbrain organoids with an SNCA gene triplication display dopamine-dependent alterations in network activity

This study shows that midbrain organoids with SNCA gene triplication exhibit PD-like neural activity changes, which can be reversed by dopamine agonists.

Sex-focused analyses of M83 A53T hemizygous mouse model with recombinant human alpha-synuclein preformed fibril injection identifies female resilience to disease progression: A combined magnetic resonance imaging and behavioural study.

The paper investigates sex differences in aSyn pathology progression in M83 mice using MRI and behavioral analysis, finding female resilience to neurodegeneration despite earlier motor symptom onset in males.

Cell type transcriptomics reveal shared genetic mechanisms in Alzheimer's and Parkinson's disease

The paper identifies shared molecular mechanisms between Alzheimer's and Parkinson's disease by analyzing gene co-expression at sub-cell-type resolution using single-nucleus datasets.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons

This study investigates the role of cathepsin B in Parkinson's disease by analyzing genetic variants and manipulating catB function in cell models to assess its impact on lysosomal activity and alpha-synuclein clearance.

Interpretable machine learning classifiers implicate GPC6 in Parkinson's disease from single-nuclei midbrain transcriptomes

The paper uses machine learning on single-nuclei RNA sequencing data to identify GPC6 as a genetic risk factor for Parkinson's disease.

ScRNAbox: Empowering Single-Cell RNA Sequencing on High Performance Computing Systems

scRNAbox provides an HPC-friendly scRNA-seq analysis pipeline with quality control, integration, clustering, annotation, and differential expression analysis.

Multi-ancestry genome-wide meta-analysis in Parkinson's disease

This paper conducts a multi-ancestry genome-wide meta-analysis of Parkinson's disease, identifying 78 independent loci and 23 genes associated with PD risk.

A deep learning convolutional neural network distinguishes neuronal models of Parkinson's disease from matched controls

This study uses a convolutional neural network to classify Parkinson's disease models from control cells with high accuracy using microscopy images.

Global Parkinson's Genetics Program (GP2) Complex Network Protocol: Defining the causes of sporadic Parkinson's disease

The paper outlines the protocol for integrating genetic and clinical data from a global cohort of over 150,000 participants to study the genetic causes of sporadic Parkinson's disease.

Identification of novel variants, genes and pathways potentially linked to Parkinson's disease using machine learning

The paper uses machine learning to identify candidate genes, variants, and pathways potentially linked to Parkinson's disease from GWAS loci and genomic data.

A dual hit of α-synuclein internalization and immune challenge leads to formation and maintenance of Lewy body-like inclusions in human dopaminergic neurons

The paper shows that combining α-synuclein fibrils with immune challenges causes Lewy body-like inclusions in human dopaminergic neurons, while cortical neurons do not form such inclusions.